Is PROKR2 p.Pro302Ser (c.904C>T) pathogenic?

PROKR2 p.Pro302Ser (c.904C>T) is classified Uncertain significance in PROKR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-27). AlphaMissense: ambiguous (0.3654); Very rare (popmax 0.00801%, afr).

How common is PROKR2 p.Pro302Ser (c.904C>T) in the general population?

PROKR2 p.Pro302Ser (c.904C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about PROKR2 p.Pro302Ser (c.904C>T)?

AlphaMissense predicts ambiguous (score 0.3654) — an in-silico prediction, not a clinical call.

PROKR2 p.Pro302Ser

c.904C>T · rs199958585 · VCV2910459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Computational evidence

Protein change
AlphaMissense	0.3654	ambiguous
REVEL	0.396	indeterminate
SaProt	LLR -10.97	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.0097 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,930 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000743% 12/1,614,118 alleles · very rare exomes 8/1,461,892 · genomes 4/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,488
European (non-Finnish)	0.000508%	196,674

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PROKR2
Protein: p.Pro302Ser
Coding: c.904C>T
MANE Select: NM_144773
dbSNP: rs199958585
Type: single nucleotide variant
Location: chr20:5302291 (GRCh38)
Gene constraint: LOEUF 1.492 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.50

Full PROKR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PROKR2 p.Arg164Gln Likely pathogenic ★★ same type
PROKR2 p.Glu231Lys Likely pathogenic ★★ ⚠ same type
PROKR2 p.Tyr316Ter Likely pathogenic ★★ same type
PROKR2 p.Ala103Val Uncertain significance ★★ ⚠ same type
PROKR2 p.Ala129Thr Uncertain significance ★★ ⚠ same type
PROKR2 p.Ala156Thr Uncertain significance ★★ same type
PROKR2 p.Arg135Cys Uncertain significance ★★ ⚠ same type
PROKR2 p.Arg248Trp Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prokr2-p-pro302ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown